5-HT受体亚型专一性药物与心血管系统

1986年Bradley等建立的5-HT受体分类系统形成了以后鉴定5-HT受体的基础。他们提出有三种主要的5-HT受体:5-HT2及5-HT3,在药理学上可用选择性拮抗剂来确定;而5-HT1类的受体是借助于选择性激动剂及非选择性拮抗剂来确定。5-HT1类受体的结合位点可以进一步划分成四种不同的亚类,

Androgen actions on endothelium functions and cardiovascular diseases

The roles of androgens on cardiovascular physiology and pathophysiology are controversial as both beneficial and detrimental effects have been reported. Although the reasons for this discrepancy are unclear, multiple factors such as genetic and epigenetic variation, sex-specificity, hormone interactions, drug preparation and route of administration may contribute. Recently, growing evidence suggests that androgens exhibit beneficial effects on cardiovascular function though the mechanism remains to be elucidated. Endothelial cells （ECs） which line the interior surface of blood vessels are distributed throughout the circulatory system, and play a crucial role in cardiovascular function. Endothelial progenitor cells （EPCs） are considered an indispensable element for the reconstitution and maintenance of an intact endothelial layer. Endothelial dysfunction is regarded as an initiating step in development of atherosclerosis and cardiovascular diseases. The modulation of endothelial functions by androgens through either genornic or nongenomic signal pathways is one possible mechanism by which androgens act on the cardiovascular system. Obtaining insight into the mechanisms by which androgens affect EC and EPC functions will allow us to determine whether androgens possess beneficial effects on the cardiovascular system. This in turn may be critical in the prevention and therapy of cardiovascular diseases. This article seeks to review recent progress in androgen regulation of endothelial function, the sex-specificity of androgen actions, and its clinical applications in the cardiovascular system.

ACE2/Ang-(1-7) signaling and vascular remodeling

The renin-angiotensin system(RAS)regulates vascular tone and plays a critical role in vascular remodeling,which is the result of a complex interplay of alterations in vascular tone and structure.Inhibition of the RAS has led to important pharmacological tools to prevent and treat vascular diseases such as hypertension,diabetic vasculopathy and atherosclerosis.Angiotensin converting enzyme 2(ACE2)was recently identified as a multifunctional monocarboxypeptidase responsible for the conversion of angiotensin(Ang)II to Ang-(1-7).The ACE2/Ang-(1-7)signaling has been shown to prevent cellular proliferation,pathological hypertrophy,oxidative stress and vascular fibrosis.Thus,the ACE2/Ang-(1-7)signaling is deemed to be beneficial to the cardiovascular system as a negative regulator of the RAS.The addition of the ACE2/Ang-(1-7)signaling to the complexities of the RAS may lead to the development of novel therapeutics for the treatment of hypertension and other vascular diseases.The present review considers recent findings regarding the ACE2/Ang-(1-7)signaling and focuses on its regulatory roles in processes related to proliferation,inflammation,vascular fibrosis and remodeling,providing proof of principle for the potential use of ACE2 as a novel therapy for vascular disorders related to vascular remodeling.

Pharmacological effects of Astragaloside IV: a literature review

OBJECTIVE: To review the pharmacological effects and mechanisms of action of Astragaloside IV in Huangqi (Radix Astragali Mongolici). METHODS: Aticles focusing on Astragaloside IV in English and Chinese in databases were collected and reviewed in order to summarize the latest extraction separation, pharmacokinetics, and the pharmacological effects of astrageloside IV. RESULTS: Protective effects of Astrageloside IV on the cardiovascular system, immune, digestive, nervous system were identified, and the action mechanisms were associated with regulation of the calcium balance, anti-oxydant, antiapoptosis, antivirus, and so on. CONCLUSION: Astrageloside IV has broad application prospects, especially in cardiovascular diseases, digestive diseases, cancer and other modern high incidence, high-risk diseases, and could be developed as a medicine.

Analysis on care outcome of patients with polytrauma and coma

Objective ： To make further improvement of outcome of patients with polytrauma and coma. Methods： The data of 3 361 patients （2 378 males and 983 females, aged from 5-95 years, 38. 2 years on average） with severe polytrauma and coma admitted to Chongqing Emergency Medical Center （Level I Trauma Center ）, Chongqing, China, from November 1978 to December 2004 were analyzed retrospectively in this study. Results： The overall survival rate and mortality were 93.2%（3 133/3 361 ）and 6.8%（228/3 361 ）, respectively. The mortalities in patients with coma duration 〈 1 hour and combined with neural dysfunction and in patients with coma duration ≥ 1 hour and combined with or without neural dysfunction were signifieantly higher than that of those with coma duration 〈 1 hour but without neural dysfunction [39.5%（136/344）vs 3.0%（92/3 017）, P 〈0.01]. There existed significant differences in GCS, ISS, and revised trauma score （RTS） between the death group and the survival group （P 〈 0. 01 ）. RTS was in good correspondence with patient＇ s pathophysiological status and outcome in patients with multiple trauma and coma for different groups of systolic blood pressure （SBP）. The mortality in patients with SBP 〈90 nun Hg was significantiy higher than that of those with SBP ≥ 90 mm Hg [ 33. 3 % （68/204） vs5.1%（160/3 157）, P 〈0.01]. The mortality in polytranma patients combined with serious head injury （AIS≥3） was8.2%, among which, 76.5% died from lung complications. The morbidity rate of lung complications and mortality rate increased in patients with head injury complicated with chest or abdomen injury （23.9%, 61.1% vs 27.3 %, 50.0 % ）. The mortality reached up to 61.9 % in patients complicated with severe head, chest and abdomen injuries simultaneously. Conclusions： It plays a key role to establish a fast and effective trauma care system and prompt and definite surgical procedures and to strengthen the management of complications for improving the survival rate of patients with severe palytrauma and coma.

Intermedin/adrenomedullin2: an autocrine/paracrine factor in vascular homeostasis and disease

Intermedin(IMD)or adrenomedullin 2 is a novel peptide related to the calcitonin gene-related peptide(CGRP)family.Via calcitonin receptor-like receptor/receptor activity modifying proteins,the common receptor complexes of CGRP,IMD exerts a wide range of biological effects,especially regulation of cardiovascular homeostasis.Proteolytic processing of a larger IMD precursor yields a series of biologically active C-terminal fragments,IMD1–53,IMD1–47 and IMD8–47.IMD and its receptors are present in the cardiovascular system,and IMD is present at low levels in plasma.In the cardiovascular system,IMD has multiple functions such as regulation of blood pressure and cardiac function,pro-angiogenesis,endothelial barrier function protection,anti-oxidative stress,and anti-endoplasmic reticulum stress.IMD participates widely in the pathogenesis of atherosclerosis,hypertension,pulmonary arterial hypertension and vascular calcification.It is a vascular regulatory factor of homeostasis and a vital endogenous protective factor against vascular diseases.